Abstract
Unilateral ligation of the tendon of anterior superficial part of rat masseter muscle (TASM) leads to long-lasting allodynia. Sex differences in peripheral mu-opioid receptor (MOR)-mediated analgesia under persistent myogenic pain are not well understood. In this study, we examined (1) whether locally applied MOR agonists attenuate persistent pain following TASM ligation in a sex dependent manner, (2) whether there are sex differences of MOR expression changes in rat trigeminal ganglia (TG). The effects of MOR agonist, D-Ala2, N–Me-Phe4, Gly5-ol]-Enkephalin acetate salt (DAMGO), were assessed 14 days after TASM ligation in male, female and orchidectomized (GDX) male rats. MOR mRNA and protein levels in TG 14 days following tendon ligation were also determined. The mechanical thresholds of the injured side were significantly decreased in both male and female rats, from 3 days to 28 days after TASM ligation. A10 μg DAMGO significantly attenuated allodynia in male rats. A 10-fold higher dose of DAMGO was required in female and GDX male rats to produce the level of anti- allodynia achieved in male rats. The level of MOR mRNA in TG from male rats was significantly greater 14 days after TASM ligation compared with the sham-operated male rats, but not from female and GDX male rats. After TASM ligation, males had significantly more MOR immunoreactivity in TG compared to sham-operated males. The MOR levels increased to 181.8% of the sham level in male rats receiving tendon injury. But there was no significant change in female rats receiving tendon injury compared to the sham female rats. Taken together, our data suggest that there were sex differences in the effects of peripheral MOR agonists between male and female rats under TASM ligation developing long-lasting pain condition, which is partly mediated by sex differences in the changes of MOR expressions and testosterone is an important factor in the regulation of MOR.
Highlights
The functional role of peripheral mu-opioid receptor (MOR) in producing anti-nociception as well as anti-hyperalgesia has been demonstrated in various pain models [1,2], and is partly mediated by the significant increase in the MOR mRNA and protein levels in dorsal root ganglia [3]
Our data suggest that there were sex differences in the effects of peripheral MOR agonists between male and female rats under TASM ligation developing long-lasting pain condition, which is partly mediated by sex differences in the changes of MOR expressions and testosterone is an important factor in the regulation of MOR
We investigate (1) whether locally applied MOR agonists attenuate persistent pain following ligation of the tendon of masseter muscle in a sex dependent manner, (2) whether there are sex differences of MOR expression changes in rat trigeminal ganglia (TG) in a TASM ligation-induced long-lasting pain condition, (3) whether testosterone involves in analgesia in male rats
Summary
The functional role of peripheral mu-opioid receptor (MOR) in producing anti-nociception as well as anti-hyperalgesia has been demonstrated in various pain models [1,2], and is partly mediated by the significant increase in the MOR mRNA and protein levels in dorsal root ganglia [3]. The currently used orofacial inflammatory models generate pain lasting from several hours to 2 weeks; they are not suitable for studying the long persistency of chronic myogenic pain in TMJ disorders. Unilateral ligation of the tendon of anterior superficial part of rat masseter muscle (TASM) leads to long-lasting and constant mechanical allodynia [7,8], which is useful in studying the chronicity of myogenic pain. We investigate (1) whether locally applied MOR agonists attenuate persistent pain following ligation of the tendon of masseter muscle in a sex dependent manner, (2) whether there are sex differences of MOR expression changes in rat trigeminal ganglia (TG) in a TASM ligation-induced long-lasting pain condition, (3) whether testosterone involves in analgesia in male rats
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